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BACKGROUND: Transperineal percutaneous laser ablation (TPLA) has been proved a feasible and minimally invasive treatment for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). However, the comparison with other therapeutic options, in particular transurethral resection of the prostate (TURP), the most widely used and gold standard surgical method for BPH patients, remained absent. METHODS: Totally 51 BPH patients treated between 6/2019 and 12/2021 who had maximum urinary flow rate (Qmax) ≤15 mL/s and international prostate symptom score (IPSS) ≥8 were enrolled and randomly assigned to TURP or TPLA group at the ratio 1:1. TPLA was conducted with Esaote MyLab Twice equipped with flexible optical fiber, and TURP was performed by Olympus UES-40 SurgMaster System under standard procedure. The results were compared at 1, 3, 6 and 12 months after the operation. The efficacy endpoints included IPSS, Qmax, quality of life (QoL), European questionnaire-five dimensions (EQ-5D), residual urine volume (RUV), international index of erectile function-5 (IIEF-5) and ejaculatory dysfunction score. The safety endpoints included the incidence of complications, blood loss, visual analogue score (VAS) of pain, and catheter indwelling time. RESULTS: The IPSS decreased by 14.17±6.13 at 3 months after TPLA, and by 13.19±5.86 after TURP (P=0.706). The complication rate of TPLA and TURP was 16% and 19.23% respectively (P=0.811).TPLA proved less Intraoperative blood loss (6.84±3.1mL,P＜0.001) and better ejaculatory protection within 6 months (P＜0.05). TURP has advantages in catheter indwelling time(P=0.012) and Qmax within 6 months(P＜0.05). CONCLUSIONS: TPLA is comparable to TURP in the symptom relief of BPH patients, and with shorter operation time, less invasiveness and better protection, which may be more suitable for patients intolerant to TURP, or with underlying diseases such as anemia.

The overexpression of heat shock proteins (HSPs) in tumor cells can activate inherent defense mechanisms during hyperthermia-based treatments, inducing thermoresistance and thus diminishing the treatment efficacy. Here, we report a distinct “non-inhibitor involvement” strategy to address this issue through engineering a calcium-based nanocatalyst (G/A@CaCO3-PEG). The constructed nanocatalyst consists of calcium carbonate (CaCO3)-supported glucose oxidase (GOD) and 2D antimonene quantum dots (AQDs), with further surface modification by lipid bilayers and polyethylene glycol (PEG). The engineered G/A@CaCO3-PEG nanocatalyst features prolonged blood circulation, which is stable at neutral pH but rapidly degrades under mildly acidic tumor microenvironment, resulting in rapid release of drug cargo in the tumor microenvironment. The integrated GOD effectively catalyzes the depletion of glucose for reducing the supplies of adenosine triphosphate (ATP) and subsequent down-regulation of HSP expression. This effect then augments the therapeutic efficacy of photothermal hyperthermia induced by 2D AQDs upon irradiation with near-infrared light as assisted by reversing the cancer cells’ thermoresistance. Consequently, synergistic antineoplastic effects can be achieved via low-temperature photothermal therapy. Systematic in vitro and in vivo evaluations have demonstrated that G/A@CaCO3-PEG nanocatalysts feature potent antitumor activity with a high tumor-inhibition rate (83.92%). This work thus paves an effective way for augmenting the hyperthermia-based tumor treatments via restriction of the ATP supply., Graphical abstract Image 1, Highlights • A concept of “non-inhibitor involvement” strategy is proposed for reversing tumor cell thermoresistance. • The ingenious integration of calcium biomineral and single-element 2D antimonene quantum dots was firstly demonstrated. • The engineered nanocatalysts highlights the high potential of the ATP restriction and HSP inhibition in cancer treatment. • This work provides an effective strategy for augmenting hyperthermia-based treatments efficacy.

Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks specific treatment. Fibroblast growth factor 21 (FGF21) has been proved to have cardioprotective effect in DCM. However, the insufficient cardiac delivery effect of FGF21 limits its application in DCM. Therefore, to improve the therapeutic efficacy of FGF21 in DCM, an effective drug delivery system is urgently required. In this study, perfluoropropane (C3F8) and polyethylenimine (PEI)-doped poly (lactic-co-glycolic acid) (PLGA) nanobubbles (CPPNBs) were synthesized via double-emulsion evaporation and FGF21 was efficiently absorbed (CPPNBs@FGF21) via the electrostatic incorporation effect. CPPNBs@FGF21 could effectively deliver FGF21 to the myocardial tissue through the cavitation effect under low-frequency ultrasound (LFUS). The as-prepared CPPNBs@FGF21 could efficiently load FGF21 after doping with the cationic polymer PEI, and displayed uniform dispersion and favorable biosafety. After filling with C3F8, CPPNBs@FGF21 could be used for distribution monitoring through ultrasound imaging. Moreover, CPPNBs@FGF21 significantly downregulated the expression of ANP, CTGF, and caspase-3 mRNA via the action of LFUS owing to increased FGF21 release, therefore exhibiting enhanced inhibition of myocardial hypertrophy, apoptosis, and interstitial fibrosis in DCM mice. In conclusion, we established an effective protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM. Statement of significance: Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks effective clinical treatments. Fibroblast growth factor 21 (FGF21) can protect cardiomyocytes from diabetic damage, but insufficient cardiac drug delivery limits the application of FGF21 in DCM. In this study, perfluoropropane (C3F8) and polyethylenimine (PEI)-doped poly (lactic-co-glycolic acid) (PLGA) nanobubbles loaded with FGF21 (CPPNBs@FGF21) were developed for the prophylactic treatment of DCM. CPPNBs@FGF21 could effectively deliver the FGF21 to the myocardial tissue through the cavitation effect of low-frequency ultrasound (LFUS). Our results indicated that CPPNBs@FGF21 combined with LFUS could significantly down-regulate the expressions of ANP, CTGF, and caspase-3 mRNA, and as a result, it prevented the myocardial hypertrophy, apoptosis, and interstitial fibrosis of DCM mice. Overall, we established an effective protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM.

Clinical and experimental findings have disclosed a high recurrence rate after radiofrequency ablation (RFA), which might be due to the dissemination of malignant cells into the vasculature during ablation. Here, we apply in vivo flow cytometry (IVFC) to monitor circulating tumor cells (CTCs) while performing ablation in a real-time and noninvasive way in an orthotopic model of prostate cancer. We report that CTCs are dramatically increased during RFA. The CTCs induced by ablation eventually translate into enhanced distant metastasis and reduced survival as compared to resection. Immunofluorescence analysis reveals that RFA significantly increases the infiltration of tumor-associated macrophages (TAMs) in the lung. Our study thus suggests that the ablative procedure of prostate tumors causes immediate tumor cell dissemination and increases distant metastasis.

Magnetic hyperthermia therapy (MHT) has been considered as an excellent alternative for treatment of deep tumor tissue; however, up-regulation of heat shock proteins (HSPs) impairs its hyperthermal therapeutic effect. Reactive oxygen species (ROS) and competitive consumption of ATP are important targets that can block excessive HSP generation. We developed a magnetic nanocatalytic system comprised of glucose oxidase (GOD)-loaded hollow iron oxide nanocatalysts (HIONCs) to drive starvation-chemodynamic-hyperthermia synergistic therapy for tumor treatment. The Fe2+ present in HIONCs contributed to ROS generation via the Fenton reaction, relieving thermo-resistance and inducing cell apoptosis by chemodynamic action. The Fenton effect was enhanced through the conditions created by increased MHT-related temperature, GOD-mediated H2O2 accumulation, and elevated tumor microenvironment acidity. The HIONCs catalase-like activity facilitated conversion of H2O2 to oxygen, thereby replenishing the oxygen levels. We further demonstrated that locally injected HIONCs-GOD effectively inhibited tumor growth in PC3 tumor-bearing mice. This study presents a multifunctional nanocarrier system driving starvation-chemodynamic-magnetic-thermal synergistic therapy via ROS and oxygen modulation for prostate tumor treatment.

Ferroptosis is a regulated form of necrotic cell death that involves the accumulation of lipid peroxide (LPO) species in an iron- and reactive oxygen species (ROS)-dependent manner. Previous investigations have reported that ferroptosis-based cancer therapy can overcome the limitations of traditional therapeutics targeting the apoptosis pathway. However, it is still challenging to enhance the antitumor efficacy of ferroptosis due to intrinsic cellular regulation. In this study, a ferroptosis-inducing agent, i.e., chlorin e6 (Ce6)-conjugated human serum albumin-iridium oxide (HSA-Ce6-IrO

With the rapid development of micro/nanomanufacturing technology, a variety of multifunctional micro/nanorobots have emerged. In particular, magnetic actuation‐based micro/nanorobots have attracted much interest due to their advantages of untethered contact, remote control, noninvasiveness, and high tissue‐penetrating capability. Various magnetic micro/nanorobots have been designed and applied in biomedicine, which indicates the great potential of clinical transformation. This article reviews the new advancements of engineering magnetic micro/nanorobots for versatile biomedical applications, ranging from targeted delivery, minimally invasive surgery, cellular and intracellular measurement, and intelligent sensing to detoxification and antibacterial applications. The controllability, visualization, and biosafety aspects of magnetically manipulated micro/nanorobots are summarized. In particular, the challenges being faced are discussed to outlook future prospective development.

Cardiomyocyte hypertrophy is a physiological adaptation used in an attempt to augment or preserve cardiac function for short periods. Long-term cardiomyocyte hypertrophy often progresses to heart failure. Previous studies have presented comprehensive mechanisms underlying cardiomyocyte hypertrophy, such as signaling pathways, marker genes, and marker miRNAs or lncRNAs. However, the mechanism in RNA level is still unclear. In this study, we used the whole transcriptome technology on cardiomyocety hypertrophy cells, which were cultured with a high concentration of d-glucose. Many differentially expressed markers, including genes, lncRNAs, miRNAs, and circRNAs were identified. Further quantitative real-time PCR verified the highly specific expressed genes, such as Eid1, Timm8b, Mrpl50, Dusp18, Abrc1, Klf13, and Igf1. Moreover, the functional pathways were also enriched with the differentially expressed lncRNA, miRNA, and circRNA. Our study gives new insights into cardiomyocyte hypertrophy and makes great progress in comprehending its mechanism.

Gas therapy as an emerging therapeutic modality for cancer treatment is still facing critical challenges such as precise delivery and controllable release of therapeutic gas. Herein, we report a "tumor-microenvironment remodeling" strategy for in situ sustained release of CO gas and magnetic resonance imaging (MRI)-monitored targeted/synergistic cancer gas/starvation nanotherapy by engineering cascade biodegradable nanocatalyst. The nanocatalyst integrates the enzyme catalyst glucose oxidase (GOD) and H2O2-sensitive molecule manganese carbonyl (MnCO) entrapped biodegradable hollow mesoporous organosilica nanoparticles (HMONs). Especially, GOD is initially exploited as a gatekeeper, followed by surface engineering with arginine-glycine-aspartic acid (RGD) for specifically targeting αvβ3 integrin-overexpressed cancer cells. The GOD is dissociated under reduced pH to release the loaded MnCO, and sequentially produce gluconic acid and H2O2 to remodel the TME for facilitating the in situ generation of CO/Mn2+. As systematically demonstrated both at cellular level and in an animal tumor xenograft model, the engineered nanocatalyst achieves superior theranostics performance via combinatorial CO gas and starving-like nanotherapy. This work provides an effective strategy for augmenting CO-mediated antitumor efficacy by remodeling the tumor microenvironment.

Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks specific treatment. Fibroblast growth factor 21 (FGF21) has been proved to have cardioprotective effect in DCM. However, the insufficient cardiac delivery effect of FGF21 limits its application in DCM. Therefore, to improve the therapeutic efficacy of FGF21 in DCM, an effective drug delivery system is urgently required. In this study, perfluoropropane (C

Despite their impressive plasmonic photocatalytic activity, nanosized silver and silver halides always suffer from serious agglomeration and photocorrosion, thus are severely restricted in the practical wastewater restoration applications. The design and realization of plasmonic heterojunction nanostructures is an effective way to solve this stability problem, yet the ideal plasmonic catalyst dispersion and immobilization remains a great challenge. In this work, a highly immobilized Ag@AgCl/g-C3N4 plasmonic photocatalyst was developed through a rational in-situ implanting approach, in which the Ag can be homodispersely distributed and strongly coupled with prefixed Cl sites on g-C3N4 nanosheets (CNNS). The X-ray diffraction (XRD) pattern, X-ray photoelectron spectroscopy (XPS) spectra and element mapping images clearly proved the homodispersely distribution of nanosized Ag@AgCl on the CNNS. The optimal Ag@AgCl-3/CNNS plasmonic photocatalyst with a narrow band gap of 2.45 eV and large specific surface area of 52.9 m2/g performs well in model pharmaceutical wastewater bleaching reactions under visible light. More importantly, the Ag@AgCl-3/CNNS show good stability compared with the conventional inhomogeneously coupled AgCl/g-C3N4 control as verified by their ultralow silver leakage rate in water (0.00152 mg/g·d, accounts 6.9% that of the control) and a much lower corrosion current density (Icorr = 1.63 vs. 3.45 μA), recorded by Tafel slopes. The synergetic effect of surface plasmon resonance effect of nanosized Ag@AgCl with strong visible light harvesting ability and strong coupling between Ag@AgCl and exfoliated porous g-C3N4 nanosheets can support the fast separation of photogenerated electron–hole pairs, thus significantly improving the photocatalytic efficiency in the bleaching of antibiotic pollutants and bacteria. This work affords the great potential of the rational in-situ implanting design for high-performance and stable plasmonic photocatalysts.

Aim: To evaluate the diagnostic accuracy of real-time elastography as a method for detecting prostate cancer.Material and methods: Relevant studies applying real-time elastography as the diagnostic modality and biopsy as the reference standard, published by March 1, 2018 were retrieved from PubMed, EMBASE, Web of Science and Cochrane Library databases. Two independent reviewers inspected all these articles to confirm the matching of the inclusion criteria. One reviewer with methodological expertise extracted the data from the included studies. Sensitivity, specificity and diagnostic odds ratio (DOR) were used to obtain overall estimates. Randomized effect method, meta-regression and subgroup analysis were performed.Results: Twenty-four studies out of 1156 identified articles met the inclusion criteria. Three groups were set: analysisby patient (Group 1), by core (Group 2), and by image (Group 3) and subgroups set in Group 1. The pooled estimate ofreal-time elastography sensitivity/ specificity/ DOR calculated with the identical P-value 0.00. Within subgroups “Asia” and“PSA>=10 ng/ml”, the pooled sensitivity, specificity and DOR were 0.83, 0.65 (p=0.01, I2=73.40%; p=0.02, I2=69.5%), 0.80, 0.82 (p=0.66, I2=0.00%; p=0.58, I2=0.00%) and 20.2, 8.67 (p=0.09, I2=54.2%; p=0.20, I2=35.5%), respectively. In these three groups, the areas under the SROC curve were 0.7417, 0.9246, and 0.6213 independently.Conclusions: Real-time elastography is a promising, reliable modality for the non-invasive diagnosis of patients with prostate cancer. The diagnostic accuracy of real-time elastography correlates tightly to the presence of higher PSA level and may help avoid unnecessary biopsy. It seems to be a useful tool in systemic biopsy.

Diabetic cardiomyopathy (DCM) is one of the major causes of morbidity and mortality in diabetic patients. Recent studies have demonstrated an increased level of fibroblast growth factor 21 (FGF21) in the plasma of DCM patients, and FGF21 has been proven to be a cardiovascular protector of the heart. The present study aimed to further investigate the pathogenic role of FGF21 in DCM, hypothesizing that a lack of FGF21 may promote the progression of DCM by regulating the lipid metabolism, cardiac hypertrophy and cardiac fibrosis, thus deteriorating the cardiac dysfunction. A total of 44 mice were randomly assigned into the normal (n=6), DCM (n=6), normal + scrambled siRNA (n=6), DCM + scrambled siRNA (n=6), normal + FGF21 siRNA (n=10) and DCM + FGF21 siRNA (n=10) groups. Type 1 diabetes mellitus was induced to mice in the DCM groups by streptozotocin injection, while FGF21 expression was inhibited by FGF21 siRNA. Normal and DCM mice administrated with scrambled siRNA were respectively regarded as the controls for the normal + FGF21 siRNA and DCM + FGF21 siRNA groups. In the DCM group, FGF21 inhibition promoted cardiac hypertrophy and fibrosis, and the expression levels of their indicators, including atrial natriuretic factor, α-skeletal actin, collagen type I and III, and transforming growth factor-β, increased, leading to further decreased cardiac function. In addition, FGF21 inhibition in DCM mice elevated the quantity of lipid droplets and the concentration of heart triglycerides, plasma triglycerides and cholesterol levels, accompanied by downregulation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and upregulation of cluster of differentiation (CD)36. Thus, the results indicated that FGF21 inhibition exacerbates the cardiac dysfunction by aggravating the lipid accumulation through regulating the expression levels of PGC-1α and CD36. In conclusion, it is suggested that FGF21 may be a potentially useful agent in the treatment of DCM.

The low delivery efficiency of nanoparticles to solid tumors greatly reduces the therapeutic efficacy and safety which is closely related to low permeability and poor distribution at tumor sites. In this work, an “intrinsic plus extrinsic superiority” administration strategy is proposed to dramatically enhance the mean delivery efficiency of nanoparticles in prostate cancer to 6.84% of injected dose, compared to 1.42% as the maximum in prostate cancer in the previously reported study. Specifically, the intrinsic superiority refers to the virus‐mimic surface topology of the nanoparticles for enhanced nano–bio interactions. Meanwhile, the extrinsic stimuli of microbubble‐assisted low‐frequency ultrasound is to enhance permeability of biological barriers and improve intratumor distribution. The enhanced intratumor enrichment can be verified by photoacoustic resonance imaging, fluorescence imaging, and magnetic resonance imaging in this multifunctional nanoplatform, which also facilitates excellent anticancer effect of photothermal treatment, photodynamic treatment, and sonodynamic treatment via combined laser and ultrasound irradiation. This study confirms the significant advance in nanoparticle accumulation in multiple tumor models, which provides an innovative delivery paradigm to improve intratumor accumulation of nanotherapeutics., This work proposes the combination of intrinsic optimization the nanostructure as virus‐mimic surface topology to enhance nano–bio interactions and extrinsic stimuli of microbubble‐assisted low‐frequency ultrasound to vastly improve intratumor permeability and distribution of nanoparticles in multiple cancer models. The multifunctional nanoplatform is capable with trimodal imaging to determine the optimal therapeutic timing, which demonstrates a successful combined anticancer effect.

As a promising treatment modality with spatial and temporal control, alternating magnetic field (AMF) triggered magnetic hyperthermal therapy (MHT) shows broad and promising applications to overcome the drawbacks of traditional focal therapies in combating cancer. However, the MHT efficacy is still not satisfactory with the presence of heat shock proteins (HSPs). In addition, sustained tumor hypoxia haunts practical implications for the treatment of solid tumors. Herein, a novel magnetic nanosystem composed of hollow iron oxide nanoparticles (HIONs), Fe3O4, and sonosensitizers, hematoporphyrin (HP) was rationally designed and successfully synthesized. The hollow HIONs show a large inner cavity for loading sonosensitizer molecules and possess nanozyme activity for catalyzing decomposition of endogenous overexpressed hydrogen peroxide (H2O2) to produce molecular oxygen (O2) that can overcome tumor hypoxia, thus augmenting the sonodynamic therapy (SDT)-induced highly toxic reactive oxygen species (ROS) production for efficient cancer cell apoptosis. Importantly, the generated ROS can also activates the cleavage of HSPs that further eliminate themotolerance and facilitates MHT efficacy. The synergistic catalysis-enhanced SDT efficiency and MHT effect realized most potent tumor suppression efficacy. This work develops a versatile nanoplatform for a multifunctional strategy and broadens the biological applications by rationally designing their structure.

To investigate the inter-rater reliability and agreement of the automated breast volume scanner (ABVS) and the diagnostic accuracy for differentiating malignant and benign lesions. The overall aim was to find out if the ABVS is applicable to daily clinical practice. Qualifying studies were retrieved from Pubmed, EMBASE, Cochrane Library, Biosis Preview, CBM disc and by manual search and reference lists up to 30 September 2014. Pooled sensitivity and specificity of ABVS were calculated and summary receiver operating characteristic curves were drawn. Thirteen studies were included in the meta-analysis of diagnostic accuracy and seven studies were included in the systematic review of inter-rater reliability/agreement of ABVS. For ‘diagnostic accuracy’, the pooled values of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were 92 % (95 % CI 89.9–93.8), 84.9 % (82.4–87.0), 6.172 (4.364–8.730), 0.101 (0.075–0.136), and 72.226 (39.637–131.61), respectively. For the studies of inter-rater reliability/agreement, the quality was heterogeneous and no evidenced result can be pooled. Sensitivity and specificity of ABVS for differentiating malignant and benign breast lesions were high. More sound studies focusing on inter-rater reliability/agreement of ABVS, which deeply affect the clinical utilization and generalization of ABVS, are urgently needed. • ABVS has high sensitivity and specificity in differentiating malignant and benign breast lesions. • The quality of published inter-rater reliability studies is heterogeneous. • Empirical evidence concerning the inter-rater reliability/agreement for the ABVS is rare. • Comparison studies on ABVS and other medical imaging examinations are warranted.

To investigate the role and signalling of microRNA(miR)-182 on regulating high glucose-induced cardiomyocyte hypertrophy.The candidates of miR which might potentially be involved on targeting Rac1 were predicted by applying bioinformatics analysis. The expression of all related candidates miRs was verified by real-time reverse transcription-PCR (RT-PCR) in cardiac tissues of db/db mice and db/m mice. Then the relationship between candidates miR and Rac1 was investigated with Pearson relevant analysis. Neonatal mice cardiomyocytes were cultured and divided into 2 groups: normal glucose group and high glucose group. The level of selected miR and Rac1 in two groups was detected by RT-PCR. Neonatal mice cardiomyocytes were then randomly divided into 4 groups: normal glucose group, selected microRNA mimics control group, high glucose group, high glucose plus selected miR mimics control group. The morphology of cardiomyocyte in each group was detected under light microscope. Furthermore, Rac1, β-MHC and α-SMA expressions were detected in cultured cardiomyocyte treated by high glucose for 48 h after transfecting selected miR mimics by RT-PCR and Western blot.A total of 6 miR candidates potentially targeting Rac1 were screened by bioinformatics, which were miR-182, miR-142-3p, miR-140, miR-101a, miR-429 and miR-200b. Among these candidates, miR-182 and miR-142-3p expression was significantly downregulated in cardiac tissues of db/db mice compared with db/m controls (P0.05). MiR-182 was negatively correlated with Rac1 by person analysis (r = -0.891 02). Downregulation of miR-182 and upregulation of Rac1, β-MHC, α-SMA were found in high glucose-induced cardiomyocyte. After transfection of miR-182 mimics, hypertrophic changes were significantly reduced and Rac1 as well β-MHC expression was significantly downregulated in cardiomyocyte incubated with high glucose.MiR-182 might be involved in the regulation of high glucose-induced myocardial hypertrophy process via targeting Rac1.

The beneficial effects of anthocyanins consumption on cardiovascular risk are supported by mechanistic and epidemiologic evidence. In order to explore the effects ofVacciniumberries rich in anthocyanins on serum lipids, we conducted a meta-analysis of relevant randomized controlled trials (RCTs). Sixteen studies with 1109 subjects were included in this meta-analysis. Significant heterogeneity confirmed differential effects betweenVacciniumsubclasses. The whortleberry group is significantly superior to placebo in lipids improvement. Besides, bilberry groups show significant differences in reducing LDL-C and increasing HDL-C in comparison with other treatments. For many of the other subgroups and comparison arms, there was insufficient evidence to draw conclusions about efficacy.